Miscarriage is the loss of a pregnancy before 20 weeks.
It occurs in 20 percent of all first pregnancies.
When it recurs, it is known as recurrent pregnancy
loss (RPL). It is estimated that three to five percent
of all couples desiring pregnancy will suffer RPL.
The experience of a pregnancy loss is both physically
and emotionally draining and often results in feelings
of grief. A complete evaluation is needed to identify
the causes of RPL. The majority of couples with RPL
will eventually have a successful outcome.

Overall,
approximately 12-15 percent of clinically recognized
pregnancies end in spontaneous miscarriage between
four and 20 weeks of gestation. However, the true
early pregnancy loss rate, including both clinically
recognized and unrecognized occult early miscarriages,
is two to four times greater, depending on age. Careful
studies in normally cycling healthy young women attempting
pregnancy have shown that human chorionic gonadotropin
(hCG) can often be detected transiently in the urine
of women who are otherwise quite unaware that they
had conceived and miscarried.12-14 No less than 30
percent and as much as 60 percent of all conceptions
abort within the first 12 weeks of gestation, and
at least half of all losses go unnoticed. The reproductive
loss that occurs even before a first missed menses
is substantia.

The
Causes of Loss

After a complete evaluation, the cause(s) of RPL can
be determined in two-thirds of cases. Identification
and treatment of problems significantly increases
the successful outcome in most cases. However, a complete
evaluation is necessary to identify possible problems.
This includes a medical history, history of all prior
pregnancies, review of all test results on the couple,
evaluation of social and environmental risks, and
a complete laboratory evaluation (Table 1).

Genetic
Problems

Many
couples tend to ascribe RPL to genetic factors, so
it is important to emphasize some basic points. There
are two broad types of chromosomal (genetic) abnormalities,
with the first and most common kind occurring in the
baby. This usually involves a problem unique to the
particular union of egg and sperm that resulted in
a baby that was not capable of survival. This finding
has no bearing on future pregnancies in many cases.
The second kind of chromosomal abnormality exists
in the patient or her partner and may be of concern
in all of their future pregnancies. Fortunately, this
type of genetic abnormality is discovered in only
three to five percent of couples with RPL.

Hormonal
Problems

Abnormal
ovarian function with decreased progesterone production
has been termed a "luteal phase deficiency"
and is found in five to eight percent of women with
RPL. Other hormonal deficiencies that are infrequently
associated with pregnancy loss include hypothyroidism,
an excess in the production of a hormone called prolactin,
and an imbalance in glucose and insulin. These conditions
can be treated medically.

Anatomic
Problems

Uterine
abnormalities are found in 15 to 20 percent of women
with a history of RPL. These abnormalities may be
congenital (from birth) or acquired in the course
of the woman's lifetime. Many of the congenital and
acquired abnormalities can be treated with a surgical
procedure called operative hysteroscopy. This day-surgical
procedure can be used to treat uterine septa, intrauterine
scar tissue (adhesions), and growth of smooth muscle
(leiomyomas) or glands (polyps).

Immune
Problems

The
area of immunology has become one of the most controversial
in the assessment of pregnancy loss. The causes include
autoimmune factors (immune reaction against another)
and alloimmune causes (immune reaction against another).
An example of an autoimmune disease is rheumatoid
arthritis, and an example of an alloimmune problem
would be rejection of a kidney after transplantation.
Tests for lupus anticoagulant and antiphospholipid
or anticardiolipin antibodies are clinically indicated
diagnostic tests and are abnormal in 20 percent of
women with RPL. Other tests under investigation include
natural killer (NK) cells and embryotoxic factors.
Treatment may include the use of a blood thinner,
such as heparin with baby aspirin.

Coagulation
Problems

Imbalances
in the blood clotting system have recently been recognized
as an area of importance in RPL. A number of inherited
disorders may predispose women to venous and arterial
thrombosis and block the blood flow to the developing
baby. As many as 15 percent of women with unexplained
RPL may have a blood clotting disorder. These include
deficiencies of protein C and protein S, antithrombin,
genetic mutations in factor V and factor II, and hyperhomocystinemia
that is often caused by a B vitamin deficiency. Once
identified, these conditions can be treated.

Inherited
thrombophilias resulting from genetic mutations in
clotting factors have emerged as a potentially important
cause of recurrent pregnancy loss, but a great many
women with these mutations have completely normal
reproductive performance. Why some with thrombophilias
miscarry and others do not is unknown; women with
more than one type of mutation or whose fetus inherits
the mutation may be at greater risk. At present, which
women with recurrent pregnancy loss should be screened
for thrombophilias and how they should be evaluated
remain unanswered questions. Selected screening for
the most common abnormalities in women with otherwise
unexplained recurrent pregnancy loss with a suspicious
loss after eight weeks' gestation or after detection
of fetal heart activity is reasonable, but routine
screening of all women with recurrent pregnancy loss
cannot be justified. Whereas preliminary data suggest
that combined treatment with aspirin and heparin may
improve pregnancy outcomes in women with recurrent
pregnancy loss who carry a thrombophilia, empiric
aspirin treatment in untested women has no proven
benefit.

Infectious
Problems

Infection
of the uterine lining or endometrium with slow growing
bacteria has also been associated with pregnancy loss
in five to 10 percent of women with RPL.. Certain
infectious agents have been identified more frequently
in cultures from women who have had a spontaneous
pregnancy loss. These include Ureaplasma urealyticum,
Mycoplasma hominis, and chlamydia. Other less frequent
pathogens include toxoplasma gondii, rubella, HSV,
measles, CMV, coxsackie virus and listeria monocytogenes,
though none have convincingly been shown to be associated
with ARPL. Because of the clear association with sporadic
pregnancy losses and the ease and low cost of diagnosis,
women with RPL should be cultured for the three most
frequent organisms (mycoplasma, ureaplasma, and chlamydia)
and both partners should be treated with antibiotics
if positive. Some clinicians believe that empiric
antibiotic treatment in women suspected of harboring
a genital mycoplasma infection is less costly and
less complicated than serial cultures.

Environmental
Problems

Certain
habits and occupations may be related to pregnancy
loss. It is known that tobacco use of greater than
15 cigarettes per day or alcohol use of greater than
four drinks per week will increase the chance of pregnancy
loss up to two-fold. Also, some studies have suggested
that airline attendants, women who are exposed to
chemicals in their work environment (such as hair
stylists), and women with physically strenuous work
may have an increased risk of miscarriage. Nontraumatic
exercise, intercourse, and normal daily activity do
not cause miscarriage.

During
the Evaluation

The
couple is counseled not to become pregnant while the
reason for their past pregnancy losses is being investigated.
The couple is advised to use barrier contraception
until all test results are back and any necessary
treatment plans are made. The entire process requires
about six weeks, which approximates the time of physical
healing after a loss. The emotional healing may take
considerably longer.

Dealing
with Pregnancy Loss

The
loss of a pregnancy at any stage can result in feelings
of grief. Some patients decide they do not want to
conceive again, most commonly because they feel that
they cannot deal with another loss. Some couples may
want to take a few months to sort out their feelings.
Couples with recurrent pregnancy loss usually have
a greater sense of fear anticipating what might occur
in a subsequent pregnancy. Other couples often feel
a lack of control over their lives.

It
is important to emphasize that the couple's relationship
with each other is just as important as the bond either
or both may feel with their unborn child. In many
cases, the stresses associated with pregnancy loss
may serve to strengthen the bond of marriage. In other
couples, there may be the false hope that a child
will help to save a failing marriage. One partner
may place blame on the other, or one partner might
believe the other is placing the blame on him or her.
Some individuals feel profound guilt and blame themselves
for past indiscretions. These couples may be directed
to appropriate bereavement resources for support and
counseling.